Abstract #3003

Hyperpolarized 13C MRSI of pyruvate and urea can detect immunomodulatory responses to dimethyl fumarate therapy in a model of multiple sclerosis

Caroline Guglielmetti^1,2, Christian Cordano³, Chloe Najac⁴, Ari Green³, and Myriam M Chaumeil^1,2

¹Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ³Department of Neurology, University of California San Francisco, San Francisco, CA, United States, ⁴Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Netherlands

We used hyperpolarized ¹³C magnetic resonance spectroscopic imaging (HP ¹³C MRSI) and T₁-MRI to assess dimethyl fumarate (DMF) response in a model of multiple sclerosis (MS). Gadolinium-enhanced T₁-MRI showed blood-brain-barrier breakdown, regardless of DMF treatment. In contrast, DMF therapy prevented an increase compared to untreated MS animals in HP ¹³C lactate, HP ¹³C lactate-to-pyruvate and HP ¹³C lactate-to-(pyruvate/urea) ratios. HP ¹³C MRSI findings were further correlated to pyruvate dehydrogenase activity and pro-inflammatory macrophages. Altogether, we demonstrated that HP ¹³C MRSI has potential to monitor the effect of immunomodulatory therapies within the central nervous system.

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